Open AccessDeficiency of cold‐inducible RNA‐binding protein exacerbated monocrotaline‐induced pulmonary artery hypertension through Caveolin1 and CAVIN1
Author(s) -
Liu Jingjing,
Ke Xianting,
Wang Luxin,
Zhang Yangyang,
Yang Jian
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16437
Subject(s) - pulmonary artery , endothelium , in vitro , pulmonary hypertension , artery , in vivo , medicine , biology , microbiology and biotechnology , chemistry , cardiology , biochemistry
Cold‐inducible RNA‐binding protein (CIRP) was a crucial regulator in multiple diseases. However, its role in pulmonary artery hypertension (PAH) is still unknown. Here, we first established monocrotaline (MCT)‐induced rat PAH model and discovered that CIRP was down‐regulated predominantly in the endothelium of pulmonary artery after MCT injection. We then generated Cirp ‐knockout ( Cirp ‐KO) rats, which manifested severer PAH with exacerbated endothelium damage in response to MCT. Subsequently, Caveolin1 ( Cav1 ) and Cavin1 were identified as downstream targets of CIRP in MCT‐induced PAH, and the decreased expression of these two genes aggravated the injury and apoptosis of pulmonary artery endothelium. Moreover, CIRP deficiency intensified monocrotaline pyrrole (MCTP)‐induced rat pulmonary artery endothelial cells (rPAECs) injuries both in vivo and in vitro, which was counteracted by Cav1 or Cavin1 overexpression. In addition, CIRP regulated the proliferative effect of conditioned media from MCTP‐treated rPAECs on rat pulmonary artery smooth muscle cells, which partially explained the exceedingly thickened pulmonary artery intimal media in Cirp ‐KO rats after MCT treatment. These results demonstrated that CIRP acts as a critical protective factor in MCT‐induced rat PAH by directly regulating CAV1 and CAVIN1 expression, which may facilitate the development of new therapeutic targets for the intervention of PAH.